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Identification of new targets of transcription factor POD1/TCF21 in human tumor cell cultures

Grant number: 16/12381-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2018
Effective date (End): August 31, 2020
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Claudimara Ferini Pacicco Lotfi
Grantee:Barbara dos Santos Passaia
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Transcription factors of the nuclear receptor superfamily, the steroidogenic factor 1 (SF1) and Liver Receptor Homolog (LRH1) are important in the steroidogenesis regulation, respectively, in adrenals and gonads. Moreover, both seem to be involved the tumorigenic process of these organs. Meanwhile, SF1 and LRH1 can be regulated by several factors, among them the bHLH transcription factor, POD1/TCF21. Our group has described that POD1 is downregulated in adrenocortical carcinomas, and also it can inhibit endogenous expression of SF1 and steroidogenic enzymes by binding in the E-box site of SF1 promoter of cell cultures derived from human adrenocortical carcinomas and normal rat adrenal cell culture. More recent results show that combined expression of genes POD1-BUB1B and POD1-SF1 has prognostic value in adrenocortical tumor of adult and pediatric patients, respectively. Other results showed that POD1 promotes increased gene expression of LRH1 and decreased expression of SHP, a negative regulator of LRH1 in hepatocellular carcinoma cells. Together, these and other data suggest that POD1/TCF21 may have a wider role as a regulator of transcription in tumor cells and is a candidate as tumor suppressor gene. Additionally, knowledge about its role in the adrenal tumorigenesis is still incipient. Therefore, we hypothesized that the identification of other targets controlled by POD1/TCF21 may contribute to the understanding of its importance and its role in tumor cells. Therefore, we aim sequencing the DNA immunoprecipitated of adrenal and liver tumor cells, respectively, the cell cultures NCI-H295R, ACC-T36 and HepG2 cells, transduced with lentivirus with POD1 by ChIP-Seq method, followed by validation of targets found by using ChIP-PCR, qPCR and immunoblotting. In addition, we will make a functional assessment of the viability, cell death and migration after changing the expression pattern of selected target genes through gene silencing or overexpression. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PASSAIA, BARBARA DOS SANTOS; LIMA, KELI; KREMER, JEAN LUCAS; DA CONCEICAO, BARBARA BRITO; DE PAULA MARIANI, BEATRIZ MARINHO; LIPRERI DA SILVA, JEAN CARLOS; NOGUEIRA ZERBINI, MARIA CLAUDIA; BARISSON VILLARES FRAGOSO, MARIA CANDIDA; MACHADO-NETO, JOAO AGOSTINHO; PACICCO LOTFI, CLAUDIMARA FERINI. Stathmin 1 is highly expressed and associated with survival outcome in malignant adrenocortical tumours. INVESTIGATIONAL NEW DRUGS, v. 38, n. 3, p. 899-908, JUN 2020. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.